Stem Cells and Aging

Intestine of an old fly
presenting widespread activity
of the Notch signaling pathway.

With age, the ability of most organs to maintain their function and be repaired gradually declines. This is due, at least in part, to the dramatic impact of aging on adult stem cells from flies to humans. Our work focuses on the role of conserved stress signaling pathways in the deregulation of intestinal stem cells in older animals.

In previous studies, we found that chronic activation of stress signaling pathways in the Drosophila gut causes uncontrolled stem cell proliferation and severely disrupts the function of all cells that compose the intestinal epithelium. These pathways include the JNK (Jun N-terminal Kinase) and Foxo proteins, which are conserved factors that have also been implicated in tumor formation and insulin resistance in mammals.

In addition to understanding of the age-related molecular changes, we are particularly interested in the consequences of aging stem cell populations on physiology and health. We showed that genetic manipulations that prevent the abnormal stem cell proliferation, observed in the intestine of older flies, are sufficient to prevent most of the metabolic changes associated with aging and extend the lifespan of Drosophila. These pioneer experiments demonstrated, for the first time, that longevity can be efficiently promoted by specifically altering adult stem cell behavior.

Although, we and others have started to elucidate some of the mechanisms that drive age-related tissue decay in the fly intestine, many other changes that have been observed in the aging Drosophila digestive tract remain poorly understood. Multiple projects seeking to understand these alterations are currently underway in our laboratory.

Accumulation of abnormal cells,
expressing the Green Fluorescent Protein,
in the aging fly intestine.

Measuring Drosophila lifespan.

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